title: In vitro activity of new artemisinin derivatives against Plasmodium falciparum clinical isolates from Gabon.
abstract: Nowadays, artemisinins are the mainstay of malaria treatment, but initial indications of resistance against clinically used derivatives are present. In this study, ten new artemisinin derivatives were tested in vitro against Plasmodium falciparum laboratory strains as well as clinical isolates from Gabon. All derivatives were highly active, with 50% inhibitory concentrations (IC(50) values) <13 nM in the clinical isolates. The activity of one fluoro-containing derivative did not correlate with that of the parent compound, suggesting a different activity profile. New artemisinin derivatives with different activity profiles are of special interest as they represent an important class of candidates for pre-clinical testing in clinical parasite isolates adapted to currently used artemisinins, since derivatisation is one possible strategy to prolong the clinical usefulness of this important class of antimalarials.
authors.affiliation: Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Held
authors.forename: Shahid A
authors.initials: SA
authors.lastname: Soomro
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: F Herwig
authors.initials: FH
authors.lastname: Jansen
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mordmüller
mesh_terms: D000293:Adolescent; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D005681:Gabon; D006801:Humans; D007223:Infant; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000469:parasitology*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C031327:artemisinin